Transcriptional upregulation of HSP70-2 by HIF-1 in cancer cells in response to hypoxia

✍ Scribed by Wen-Jie Huang; Li-Min Xia; Fan Zhu; Bo Huang; Chun Zhou; Hui-Fen Zhu; Bo Wang; Bin Chen; Ping Lei; Guan-Xin Shen; De-AnTian

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: French
• Weight: 481 KB
• Volume: 124
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.23906

✦ Synopsis

Abstract

Heat shock protein 70‐2 (HSP70‐2) can be expressed by cancer cells and act as an important regulator of cancer cell growth and survival. Here, we show the molecular mechanisms by which hypoxia regulate HSP70‐2 expression in cancer cells. When cells were subjected to hypoxia (1% O~2~), the expression of HSP70‐2 had a significant increase in cancer cells. Such increase was due to the direct binding of hypoxia‐inducible factor to hypoxia‐responsive elements (HREs) in the HSP70‐2 promoter. By luciferase assays, we demonstrated that the HRE1 at position −446 was essential for transcriptional activation of HSP70‐2 promoter under hypoxic conditions. We also demonstrated that HIF‐1α binds to the HSP70‐2 promoter and the binding is specific, as revealed by HIF binding/competition and chromatin immunoprecipitation assays. Consequently, the upregulation of HSP70‐2 enhanced the resistance of tumor cells to hypoxia‐induced apoptosis. These findings provide a new insight into how tumor cells overcome hypoxic stress and survive, and also disclose a new regulatory mechanism of HSP70‐2 expression in tumor cells. © 2008 Wiley‐Liss, Inc.